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News Article | May 4, 2017
Site: www.eurekalert.org

OTTAWA, ON - May 4, 2017 - A worldwide consensus co-authored by more than 40 scientists sets out ways to address research bottlenecks as the international community strives to diagnose most rare genetic diseases by 2020. A commentary paper by lead author Dr. Kym Boycott, Chair of the Diagnostics Committee of the International Rare Diseases Research Consortium (IRDiRC) and a clinical geneticist and senior scientist at the Children's Hospital of Eastern Ontario (CHEO) Research Institute, says international cooperation is needed now more than ever; despite advances in technology and decades of research, the genetic mutations behind half of the 7,000 known rare genetic diseases in the world remain a mystery. The paper, "International Cooperation to Enable the Diagnosis of all Rare Genetic Diseases", published in the American Journal of Human Genetics today, shows international enthusiasm and support for IRDiRC-recognized platforms, tools, standards and guidelines to streamline resources and accelerate progress for rare disease research. "We need new strategies to solve the unsolved," Dr. Boycott said. "Diagnosing the genes responsible for rare genetic diseases is a crucial first step towards informed patient care, giving patients a better understanding of what is causing their mysterious symptoms and helping doctors to better manage complications. We've made tremendous progress in linking rare genetic diseases to their causative biological pathways. However, the lack of data-sharing infrastructure is siloing data and hindering further discoveries. This paper for the first time sets out these pinch points so that they can be considered and addressed by the genetics community." The paper also describes the increasing challenge of discovering novel disease mechanisms and confirming their links to rare diseases. The arrival of genome-wide sequencing in 2010 resulted in a boom in the number of disease genes identified but the rate of new discoveries has plateaued or decreased in recent years. Whole Exome Sequencing, for example, allowed researchers to zone in on the exome, the portion of the genome which encodes for proteins and where 85% of mutations originate. However, as many 'straightforward' genetic links have been identified, rare diseases are getting rarer and more difficult to solve. Taila Hartley, operations director of Care4Rare based at CHEO, said some rare genetic diseases are one in a million rather than one in 300,000. Being able to confirm a genetic cause with a second patient from another country that may be recorded in a database makes a huge difference in building evidence. "With whole-exome sequencing, there was a huge boom in new genetic discoveries. We thought this was going to continue but what we've realized now is we're experiencing a plateau or even actually a decrease in the number of genes that are being identified each year. And it's because we didn't realize the international scale of data-sharing that would be necessary to solve these ultra-rare diseases," Ms. Hartley said. Dr. Boycott, co-founder of Care4Rare, a nation-wide network of doctors, scientists and clinical researchers dedicated to improving the diagnosis and treatment of rare diseases, also helped establish the Matchmaker Exchange with University of Toronto scientist Dr. Michael Brudno. The Matchmaker Exchange is a data platform that enables sharing of rare disease patient clinical and genomic information from around the world. The CHEO Research Institute coordinates the research activities of the Children's Hospital of Eastern Ontario (CHEO) and is affiliated with the University of Ottawa. Its three programs of research include molecular biomedicine, health information technology, and evidence to practice research; key research themes include cancer, diabetes, obesity, mental health, emergency medicine, musculoskeletal health, electronic health information and privacy, and genetics of rare disease. The CHEO Research Institute makes discoveries today for healthier kids tomorrow. For more information, visit http://www. . For the latest CHEO news, our Twitter handle is @CHEOhospital


News Article | February 15, 2017
Site: www.eurekalert.org

OTTAWA, ON ¬- Feb. 15, 2017 -- A promising combination of immunotherapies delivers a one-two punch to brain cancer tumours with high cure rates in mice, scientific evidence published in Nature Communications today says. Researchers at the Children's Hospital of Eastern Ontario (CHEO) in Ottawa found that a combination of drugs known as SMAC Mimetics and immune checkpoint inhibitors (ICIs) amplifies kill rates of cancer tumour cells in laboratory testing. Researchers also discovered a new mechanism by which the combination promotes long-term immunity against glioblastoma tumours. The combination therapy also proved to be highly effective against breast cancer and multiple myeloma. "These findings represent a significant evolution in our research and the field of immunotherapy. We are the first in the world to show the synergistic tumour-killing impact of combining SMAC Mimetics with immune checkpoint inhibitors for glioblastoma," said Dr. Robert Korneluk, distinguished professor at the University of Ottawa and senior scientist at the CHEO Research Institute. "You could say it takes two to tango. We believe that it takes a combination strategy to impact cancer cure rates." In 2014, a team of scientists led by Dr. Korneluk discovered that combining SMAC Mimetics with immune stimulators or live virus therapies had a synergistic or amplified tumour-killing effect that was greater than either agent on its own. Today's news shows that SMAC Mimetics also have a powerful synergistic effect with ICIs, relatively new drugs that are showing great promise in the clinic. SMAC Mimetics known as LCL161 and Birinapant were combined with ICI antibodies targeting PD-1 and CTLA-4 immune checkpoints. Eric Lacasse, a scientist at the CHEO Research Institute, said: "Two drug companies have initiated human clinical trials this year to assess the impact of this combination of SMAC Mimetics and ICIs on patients with a variety of cancers. Although it could be years before any clinical trials begin for adults or children with the deadly brain cancer, glioblastoma, we're looking forward to seeing how scientific evidence from these experimental treatments adds to our knowledge. It's an exciting, exploratory field and we hope we've hit a home run." Shawn Beug, lead author of the 2014 and 2017 papers, said: "This research heightens our understanding of the mechanics behind this double-whammy effect, which both enhances the immune response and weakens tumour cells to immune attack. We're hoping that more oncologists and biotech companies test out this combination in clinical trials as we continue to decipher how SMAC Mimetics encourage the immune system to kill cancer cells." The research was funded by the Canadian Cancer Society Research Institute, Brain Canada (with financial support from Health Canada through the Canada Brain Research Fund) and the Canadian Institutes of Health Research. In addition, the work was supported by donations to the Ottawa Regional Cancer Foundation, the Kiwanis Medical Foundation and the CHEO Foundation. The University of Ottawa--A crossroads of cultures and ideas The University of Ottawa is home to over 50,000 students, faculty and staff, who live, work and study in both French and English. Our campus is a crossroads of cultures and ideas, where bold minds come together to inspire game-changing ideas. We are one of Canada's top 10 research universities--our professors and researchers explore new approaches to today's challenges. One of a handful of Canadian universities ranked among the top 200 in the world, we attract exceptional thinkers and welcome diverse perspectives from across the globe. The CHEO Research Institute coordinates the research activities of the Children's Hospital of Eastern Ontario (CHEO) and is affiliated with the University of Ottawa. Its three programs of research include molecular biomedicine, health information technology, and evidence to practice research. Key themes include cancer, diabetes, obesity, mental health, emergency medicine, musculoskeletal health, electronic health information and privacy, and genetics of rare disease. The CHEO Research Institute makes discoveries today for healthier kids tomorrow. For more information, visit http://www.


TORONTO & MONTREAL & VANCOUVER, British Columbia--(BUSINESS WIRE)--Versant Ventures today announced that Toronto-based portfolio company Northern Biologics Inc. has executed a transformational deal that expands its pipeline and financial resources. The merger of Mosaic Biomedicals SL with Northern creates a global oncology company backed by Versant and Celgene Corp. (NASDAQ:CELG) that will advance a promising first-in-class antibody into clinical trials in 2017. This announcement also marks the fifth major investment by Versant in life science companies with Canadian operations. It closely follows last week’s debut of BlueRock Therapeutics, a stem cell company that Versant and Bayer AG jointly launched with a series A commitment of CAD$295 million, the largest ever for a Canadian life science startup. Both Northern and BlueRock are examples of harnessing top-tier science and building sustainable companies with the necessary intellectual and financial resources to bring new medicines to patients. In 2013, Versant undertook the challenge of expanding its global footprint and building a significant presence in Canada. The firm’s goal was to source the country’s best scientific opportunities and to manage those startups into successful global companies. “Since launching investment activities in Canada three years ago, our progress toward building a world-class biotech portfolio has exceeded any of our expectations,” said Brad Bolzon, Ph.D., Versant managing director. “It is a testament to the quality of the Canadian academic research community and the commitment of key stakeholders in government and the private sector to build a viable biotech ecosystem that can compete with all other global players.” Versant’s recent activity in Canada also includes portfolio company Turnstone Biologics Inc., which completed one of the largest-ever series B rounds for a Canadian biotech in November. The financing will allow Turnstone to complete ongoing clinical trials of its lead oncolytic immunotherapeutic and also launch three additional clinical programs in the coming 24 months. Like BlueRock and Northern, Turnstone’s foundation was built on scientific discoveries and new technologies developed at Canadian academic institutions. Collectively these institutions include UHN and its affiliates the McEwen Centre for Regenerative Medicine and Princess Margaret Cancer Centre, as well as the Children’s Hospital of Eastern Ontario (CHEO), McMaster University, Ontario Institute for Cancer Research (OICR), Ottawa Hospital Research Institute (OHRI), and the University of Toronto. To accelerate the development of its own investment portfolio in Canada, Versant has also established a network of laboratories across the country called Discovery Engines. These include Inception Sciences in Vancouver and Montreal, and Blueline Bioscience in Toronto. To date several new projects have been launched in the fields of oncology, ophthalmology and inflammatory diseases, some having secured series A backing from Versant and pharmaceutical partners like Bayer and Celgene. “A common theme is to catalyze the creation of companies and accelerate their maturation with our own resources and those of global pharmaceutical partners,” said Jerel Davis, Ph.D., managing director at Versant. “Our pan-Canadian portfolio spans multiple indications, with new companies built on world-class science and strategic partnerships. These startups need the capital resources to be successful, which historically had been a shortcoming of Canadian biotechs.” Canada has become a productive source of biotech investments for Versant. Versant’s Canadian footprint has grown to include three Discovery Engines that house more than 30 scientists, five fully backed companies, two seed investments and 10 academic grants supported by the firm. Together these investments represent more than CAD$500 million in committed capital from Versant, syndicate members and pharmaceutical partners. Versant Ventures is a leading healthcare investment firm committed to helping exceptional entrepreneurs build the next generation of great healthcare companies. The firm invests across the healthcare sector and at all stages of company development, with an emphasis on the discovery and development of novel therapeutics. With $1.9 billion under management and offices in North America and Europe, Versant has built a team with deep investment, operating, and scientific expertise that enables a hands-on approach to company building. Since the firm's founding in 1999, more than 65 Versant companies have achieved successful acquisitions or IPOs. For more information, please visit www.versantventures.com.


Schuler J.E.,University of Ottawa | James King W.,University of Ottawa | James King W.,Childrens Hospital of Eastern Ontario CHEO | Dayneka N.L.,CHEO | And 4 more authors.
Canadian Journal of Public Health | Year: 2011

Background: In Canada, the pH1N1 influenza vaccine is recommended for children, particularly those less than 5 years of age or with chronic underlying disease. The pH1N1 vaccine, which contains residual allergenic egg white proteins, may pose a risk for vaccination of egg-allergic children. Objective: To describe the outcome of pH1N1 influenza vaccine administration to egg-allergic children at risk for severe H1N1 disease. Design/Method: Prospective observational cohort study. Children identified as at high risk for egg allergy and H1N1 influenza were vaccinated using a two-dose split protocol in a controlled medical setting. Children were given an initial test dose; if no reaction was noted, the remainder of the dose was administered and the children were followed for allergic reactions. Those who tolerated the split dose and required a second dose of vaccine were offered vaccination four weeks later as one injection. Results: Sixty-two egg-allergic children considered at high risk for H1N1 disease received the adjuvanted pH1N1 vaccine. Egg allergy was diagnosed both clinically by an allergist and using skin and/or serum IgE testing. Within one hour of immunization, 2 children developed hives, 1 had a vasovagal response and 1 had a hypo-responsive episode. Fourteen children received the second H1N1 dose and 1 developed erythema and itching. There were no anaphylactic reactions. Conclusion: Administration of the adjuvanted pH1N1 vaccine in egg-allergic children at risk for severe H1N1 influenza was safe when performed in a two-dose split protocol in a controlled medical setting. © Canadian Public Health Association, 2011.


Menon K.,CHEO | Ward R.,CHEORI
Journal of Medical Ethics | Year: 2014

Objective: To document the legal guardian-related barriers to consent procurement, and their stated reasons for non-participation in a paediatric critical care research study. Study design: A multicentre, prospective, cohort study. Participants: Legal guardians of children who participated in a multicentre study on adrenal insufficiency in paediatric critical illness. Data were collected on all consent encounters in the main study. Methods: Screening data, reasons for consent not being obtained, paediatric risk of mortality (illness severity) scores and age were collected on all 1707 patients eligible for participation in the Adrenal Insufficiency Study. Results: The main barriers to approaching legal guardians for consent were lack of availability of the legal guardians (321/1707) and language barriers (84/1707). Legal guardians of 917 patients were approached with an overall consent rate of 42% (range 14-56% across the seven sites). 81% of the 528 legal guardians who declined consent provided an unsolicited reason for refusal. The three most commonly stated reasons were: being overwhelmed (117/429), not wanting anything else done to their child (63/429) and not wanting an additional medication (53/429). In addition, 14.2% cited research-related concerns as the reason for their non-participation. Conclusions: Barriers to consent procurement in a non-therapeutic paediatric critical care study appear to occur at many levels with lack of availability of legal guardians, and legal guardians feeling overwhelmed, being the most commonly recorded reasons. Further research into the impact of these findings on the validity and generalisability of the results of such studies is necessary prior to the development and study of future consent models.


Tremblay E.,Université de Sherbrooke | Ferretti E.,CHEO | Babakissa C.,Université de Sherbrooke | Seidman E.G.,McGill University | And 3 more authors.
Journal of Pediatric Gastroenterology and Nutrition | Year: 2011

Background and Objectives: The occurrence of many neonatal inflammatory intestinal diseases in preterm infants highlights the susceptibility of the immature intestine to responding inadequately to nutrients and microbes. A better understanding of functional intestinal development is essential for the design of optimal treatments ensuring survival and growth of premature infants. The purpose of this study was to evaluate the gene expression profiles of the human ileum and colon at mid-gestation because these 2 segments are considered to be similar at this stage and are the sites of the most frequent pathologies in preterm infants. Subjects and Methods: We compared the gene-expression profiles of human fetal small and large intestines using a cDNA microarray and analyzed the data with Ingenuity Pathway Analysis software. Results: We found that a significant proportion of the genes was differentially expressed in the 2 segments. Gene cluster analysis revealed an even higher level of transcriptional dissimilarity at the functional level. For instance, segment-specific/overexpressed gene clusters in the ileum included genes involved with amino acid, vitamin, and mineral metabolism, reflecting the higher level of maturity of the small intestine as compared with the colon in which genes involved with cell cycle, cell death, and cell signaling were the predominant clusters of genes expressed. Conclusions: Functional clustering analysis of the differentially expressed genes revealed important functional differences between the 2 segments and a relative immaturity of the colon, suggesting that already at mid-gestation, the 2 intestinal segments should be considered as 2 distinct organs. Copyright © 2011 by ESPGHAN and NASPGHAN.


PubMed | CHU de Martinique, University of Ottawa, McGill University, Hepatology & Nutrition and 5 more.
Type: | Journal: BMC medical genomics | Year: 2016

Necrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infants in neonatal intensive care units. The challenge for neonatologists is to detect early clinical manifestations of NEC. One strategy would be to identify specific markers that could be used as early diagnostic tools to identify preterm infants most at risk of developing NEC or in the event of a diagnostic dilemma of suspected disease. As a first step in this direction, we sought to determine the specific gene expression profile of NEC.Deep sequencing (RNA-Seq) was used to establish the gene expression profiles in ileal samples obtained from preterm infants diagnosed with NEC and non-NEC conditions. Data were analyzed with Ingenuity Pathway Analysis and ToppCluster softwares.Data analysis indicated that the most significant functional pathways over-represented in NEC neonates were associated with immune functions, such as altered T and B cell signaling, B cell development, and the role of pattern recognition receptors for bacteria and viruses. Among the genes that were strongly modulated in neonates with NEC, we observed a significant degree of similarity when compared with those reported in Crohns disease, a chronic inflammatory bowel disease.Gene expression profile analysis revealed a predominantly altered immune response in the intestine of NEC neonates. Moreover, comparative analysis between NEC and Crohns disease gene expression repertoires revealed a surprisingly high degree of similarity between these two conditions suggesting a new avenue for identifying NEC biomarkers.


PubMed | CHEO
Type: Journal Article | Journal: Journal of medical ethics | Year: 2014

To document the legal guardian-related barriers to consent procurement, and their stated reasons for non-participation in a paediatric critical care research study.A multicentre, prospective, cohort study.Legal guardians of children who participated in a multicentre study on adrenal insufficiency in paediatric critical illness. Data were collected on all consent encounters in the main study.Screening data, reasons for consent not being obtained, paediatric risk of mortality (illness severity) scores and age were collected on all 1707 patients eligible for participation in the Adrenal Insufficiency Study.The main barriers to approaching legal guardians for consent were lack of availability of the legal guardians (321/1707) and language barriers (84/1707). Legal guardians of 917 patients were approached with an overall consent rate of 42% (range 14-56% across the seven sites). 81% of the 528 legal guardians who declined consent provided an unsolicited reason for refusal. The three most commonly stated reasons were: being overwhelmed (117/429), not wanting anything else done to their child (63/429) and not wanting an additional medication (53/429). In addition, 14.2% cited research-related concerns as the reason for their non-participation.Barriers to consent procurement in a non-therapeutic paediatric critical care study appear to occur at many levels with lack of availability of legal guardians, and legal guardians feeling overwhelmed, being the most commonly recorded reasons. Further research into the impact of these findings on the validity and generalisability of the results of such studies is necessary prior to the development and study of future consent models.


News Article | November 23, 2016
Site: www.marketwired.com

OAKVILLE, ON--(Marketwired - November 23, 2016) - Starting Sunday, November 27, the public can help support MADD Canada and its youth education program by making a donation at any of the 657 LCBO stores throughout Ontario. Donation boxes for MADD Canada will be displayed at LCBO checkout counters until December 31. As part of LCBO's annual Giving Back In Our Community campaign, customer service representatives will also invite patrons to add a $2, $5 or $10 donation to their purchase to benefit MADD Canada. The funds raised support the production and delivery of MADD Canada's School Assembly Program, a film and in-class curriculum that educates students about the risks of impaired driving. This year's program is titled "In the Blink of an Eye". This compelling film features a combination of a fictional storyline and testimonials from real-life victims of impaired driving. This program encourages students in grades 7-12 to make responsible choices, and to not drink or take drugs and drive or ride along with someone who has. "Motor vehicle crashes are the leading cause of death among teens and young adults, and alcohol and/or drugs are involved in more than half of those crashes," said MADD Canada National President Patricia Hynes Coates. "MADD Canada's School Assembly Program opens a dialogue with young people to educate them about the dangers of impaired driving and equip them with the knowledge and tools they need to make safe and sober driving decisions." Thanks to LCBO's Giving Back In Our Community campaign, MADD Canada can deliver its School Assembly Program to approximately 500,000 Ontario students each year, at no cost to the students or the schools. "As a socially responsible community-minded retailer, LCBO is pleased to partner with MADD Canada and a variety of other worthy causes through the Giving Back In Our Community fundraising program," says LCBO President & CEO George Soleas. "Through the generosity of LCBO customers and the support of our staff, we help improve the lives of countless Ontarians and make a difference in communities across Ontario." In addition to raising funds for MADD Canada, LCBO's December Giving Back In Our Community campaign also raises funds for Ontario's four regional children's hospitals: SickKids Foundation (Toronto), McMaster Children's Hospital Foundation (Hamilton), CHEO Foundation (Ottawa) and Children's Health Foundation (London). MADD Canada and its Chapters throughout Ontario are among the 28 provincial and numerous local charities that will benefit from LCBO's province-wide donation box program in 2016. In fiscal 2015/16, LCBO raised a total of more than $10.9 million for charities through in-store fundraising, special programs and initiatives. In addition, LCBO's annual dividend transfer to the Ontario government, which totaled $1.935 billion in fiscal year 2015-16 ending March 31, 2016, excluding taxes, supports a wide range of important government programs, services and priorities, including health care and education. MADD Canada thanks the public for its support when shopping at the LCBO from November 27 - December 31.


News Article | November 2, 2016
Site: www.eurekalert.org

The Ottawa Hospital, the Children's Hospital of Eastern Ontario (CHEO), the University of Ottawa (uOttawa) and McMaster University congratulate Turnstone Biologics Inc. (Turnstone) on securing US$ 41.4 million in new private investments. Turnstone was founded in 2015 to advance the development of novel oncolytic viral immunotherapies for cancer. Its technology is based on research led by Dr. John Bell (from The Ottawa Hospital and uOttawa), Dr. Brian Lichty (from McMaster University) and Dr. David Stojdl (from CHEO and uOttawa). Turnstone's most advanced product is an oncolytic Maraba virus that is engineered to express melanoma-associated antigen A3 (MAGEA3). This is currently being tested in a clinical trial led by The Ottawa Hospital, sponsored by the Canadian Cancer Trials Group, and funded by the Ontario Institute for Cancer Research. Full results are expected to be released in 2017. More information for patients is available here. Dr. David Stojdl, senior scientist, Children's Hospital of Eastern Ontario; associate professor, University of Ottawa: "This financing is incredible validation that we're on the right track. We all want to be part of a scientific narrative that changes lives, and I believe that our immunotherapy approach is it." Dr. Brian Lichty, associate professor at McMaster University: "We have had tremendous success with our technology so far, but this financial support as a commercial venture is essential in enhancing our ability to bring it to the bedside. We know there is so much potential." Dr. John Bell, senior scientist, The Ottawa Hospital; professor, University of Ottawa: "Community support has been and will continue to be crucial for our research. However developing new therapies is extremely costly, so we also need to engage the private sector to take our research to the next level. I want to express my deep gratitude to all the people who have helped get us to this exciting place." Dr. Derek Jonker, Principal Investigator for the Maraba trial; medical oncologist, The Ottawa Hospital; professor, University of Ottawa: "We are pleased with the progress of the clinical trial so far and now have a better understanding of how patients do after receiving the dual virus vaccine therapy. We anticipate moving to phase II for patients with lung, breast and esophagogastric cancers in the near future." Dr. Martin Osmond, CEO and Scientific Director, CHEO Research Institute: "CHEO is proud that the Stojdl lab was involved in the initial discovery and development of the Maraba virus! Today it's the lead asset in Turnstone's impressive portfolio, which is nothing short of inspiring. My heartfelt congratulations to the entire team at Turnstone for this major funding milestone which boosts the trajectory towards improved patient outcomes through research." Dr. Duncan Stewart, Executive Vice-President of Research, The Ottawa Hospital; professor, University of Ottawa: "It is incredibly challenging for academic researchers to take a discovery all the way from the lab bench to the patient's bedside, so I want to offer my heartfelt congratulations to Dr. Bell and his colleagues. Their success has helped to create a culture of translational research at The Ottawa Hospital that has huge potential for patients as well as the economy." Dr. Mona Nemer, Vice-President of Research, University of Ottawa "This investment represents a major milestone in the development and translation of academic research discoveries into the clinic. The University of Ottawa congratulates Turnstone and our researchers on their success. We look forward to working with Turnstone and the research team to advance this technology further." Dr. Paul O'Byrne, Dean and Vice-President, Faculty of Health Sciences, McMaster University "Commercialization of discoveries in our academic laboratories is an important move forward to a healthy society, both economically and physically. We are extremely thrilled by the work of Dr. Lichty and other McMaster scientists, and the collaboration on this project with CHEO, The Ottawa Hospital, University of Ottawa, other supporters and now, Turnstone. This significant investment being made in Turnstone is much appreciated." Dr. Lincoln Stein, Interim Scientific Director of The Ontario Institute for Cancer Research: "The Ontario Institute for Cancer Research is proud to stimulate the groundbreaking multi-institutional research behind Turnstone, including significant financial and in-kind support enabling the current clinical trial. We congratulate the Turnstone team on attracting further investment to the benefit of both patients with cancer and the innovation economy of Ontario." Dr. Stéphanie Michaud, President and CEO, BioCanRx "On behalf of BioCanRx, I wish to extend my congratulations to Turnstone Biologics on the significant investment announced today. This announcement not only reflects the accomplishments of Turnstone but also of the advancements in the oncolytic virus platform in Canada, and around the world. These novel therapies potentially offer a unique opportunity to change the way we treat cancer patients. We are delighted to continue working with Turnstone in transitioning these important new discoveries out of the lab and into the clinic."

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